This invention relates to the culturing of biological cells and tissues and, more particularly, to a method and apparatus for cell and tissue culture in high density employing perfused blood as the nutrient source.
Biological cells and tissues cultured in vitro are commonly employed in various biomedical applications, such as, for example, in the development and production of various vaccines, and for the in vitro screening of potential anti-cancer agents prior to in vivo testing in laboratory test animals. The culture systems presently in use typically employ synthetic culture media as the source for the cell nutrients, and for the most part, are incapable of supporting high density cell growth. With such systems, it has been found to be extremely difficult to obtain substantial quantities of cultured cells and tissues which maintain their in vivo function.
Previous studies directed toward the development of more efficient tissue culture systems have led to the findings that cells can be grown in high density in an artificial capillary system where there is a high surface area for diffusion for a given cell volume, and that cells grown in high density maintain their metabolic activity, such as hormone production. It has also previously been found that certain differentiated cell lines, when grown in high density culture, maintain their in vivo function when blood is perfused through the culture system. However, use of perfused blood in tissue culture systems, particularly as the primary culture medium, presents certain problems which must be overcome. First of all, the cells or tissues being cultured must be maintained separated from the cellular components of the perfused blood, since foreign cells coming into contact with immunologically competent host cells tend to be rapidly destroyed by the host cells. Secondly, in the artificial capillary culture systems previously proposed, capillary lumen occlusion from small thrombi and debris in the perfused blood and resultant cell necrosis prevent such systems from remaining patent with respect to perfused blood for periods of time sufficiently long so as to render such systems practical.